Deep TMS on alcoholics: effects on cortisolemia and dopamine pathway modulation. A pilot study.

The hypothalamic pituitary adrenal axis and dopamine have a key role in transition from alcohol social use to addiction. The medial prefrontal cortex was shown to modulate dopaminergic activity and cortisol releasing factor (CRF) release in hypothalamic and extra-hypothalamic systems. The recent advancements in non-invasive neurostimulation technologies has enabled stimulation of deeper brain regions using H-coil transcranial magnetic stimulation (TMS) in humans. This randomized double-blind placebo-controlled pilot study aims to evaluate H-coil efficacy in stimulating the medial prefrontal cortex. Cortisolemia and prolactinemia were evaluated as effectiveness markers. Alcohol intake and craving were considered as secondary outcomes. Eighteen alcoholics were recruited and randomized into 2 homogeneous groups: 9 in the real stimulation group and 9 in the sham stimulation group. Repetitive TMS (rTMS) was administered through a magnetic stimulator over 10 sessions at 20 Hz, directed to the medial prefrontal cortex. rTMS significantly reduced blood cortisol levels and decreased prolactinemia, thus suggesting dopamine increase. Craving visual analogic scale (VAS) in treated patients decreased, as well as mean number of alcoholic drinks/day and drinks on days of maximum alcohol intake (DMAI). In the sham group there was no significant effect observed on cortisolemia, prolactinemia, mean number of alcoholic drinks/day, or drinks/DMAI. Thus, deep rTMS could be considered a potential new treatment for alcoholism.

[1]  M. Soyka,et al.  Treatment-refractory substance use disorder: Focus on alcohol, opioids, and cocaine , 2016, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[2]  A. Pascual-Leone,et al.  H-coil repetitive transcranial magnetic stimulation for treatment of temporal lobe epilepsy: A case report , 2016, Epilepsy & Behavior Case Reports.

[3]  A. Zangen,et al.  Effectiveness of Deep Transcranial Magnetic Stimulation Combined with a Brief Exposure Procedure in Post-Traumatic Stress Disorder – A Pilot Study , 2013, Brain Stimulation.

[4]  Patrice D Cani,et al.  The Loss of Metabolic Control on Alcohol Drinking in Heavy Drinking Alcohol-Dependent Subjects , 2012, PloS one.

[5]  K. Merikangas,et al.  Epidemiology of substance use disorders , 2012, Human Genetics.

[6]  F. Mora,et al.  Aging impairs the control of prefrontal cortex on the release of corticosterone in response to stress and on memory consolidation , 2012, Neurobiology of Aging.

[7]  F. Mora,et al.  Aging increases basal but not stress-induced levels of corticosterone in the brain of the awake rat , 2012, Neurobiology of Aging.

[8]  R. Krueger,et al.  Personality disorders and the 3-year course of alcohol, drug, and nicotine use disorders , 2011 .

[9]  R. Sinha,et al.  Effects of adrenal sensitivity, stress- and cue-induced craving, and anxiety on subsequent alcohol relapse and treatment outcomes. , 2011, Archives of general psychiatry.

[10]  C. Lewis,et al.  Substance use and violent behavior in women with antisocial personality disorder. , 2011, Behavioral sciences & the law.

[11]  J. Smit,et al.  Alcohol-induced Cushing syndrome. Hypercortisolism caused by alcohol abuse. , 2011, The Netherlands journal of medicine.

[12]  J. Kornhuber,et al.  Prolactin serum levels during alcohol withdrawal are associated with the severity of alcohol dependence and withdrawal symptoms. , 2011, Alcoholism, clinical and experimental research.

[13]  Rajita Sinha,et al.  Association of frontal and posterior cortical gray matter volume with time to alcohol relapse: a prospective study. , 2011, The American journal of psychiatry.

[14]  L. Parsons,et al.  Corticotropin Releasing Factor–Induced Amygdala Gamma-Aminobutyric Acid Release Plays a Key Role in Alcohol Dependence , 2010, Biological Psychiatry.

[15]  A. Zangen,et al.  Deep TMS in a resistant major depressive disorder: a brief report , 2010, Depression and anxiety.

[16]  S. Rossi,et al.  Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research , 2009, Clinical Neurophysiology.

[17]  Leor N. Katz,et al.  Deep transcranial magnetic stimulation over the prefrontal cortex: Evaluation of antidepressant and cognitive effects in depressive patients , 2009, Brain Stimulation.

[18]  G. Koob,et al.  Development of pharmacotherapies for drug addiction: a Rosetta Stone approach , 2009, Nature Reviews Drug Discovery.

[19]  A. Zangen,et al.  Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption. , 2009, Addiction.

[20]  G. Koob A Role for Brain Stress Systems in Addiction , 2008, Neuron.

[21]  G. Stuber,et al.  Corticotropin‐releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C‐dependent enhancement of Ih , 2008, The Journal of physiology.

[22]  E. Eşel,et al.  Hypothalamic–pituitary–adrenal axis activity, dehydroepiandrosterone sulphate and their relationships with aggression in early and late alcohol withdrawal , 2008, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[23]  Abraham Zangen,et al.  A randomized controlled feasibility and safety study of deep transcranial magnetic stimulation , 2007, Clinical Neurophysiology.

[24]  Z. Xu,et al.  Chronic alcohol drinking alters neuronal dendritic spines in the brain reward center nucleus accumbens , 2007, Brain Research.

[25]  Alon Amir,et al.  Three-Dimensional Distribution of the Electric Field Induced in the Brain by Transcranial Magnetic Stimulation Using Figure-8 and Deep H-Coils , 2007, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[26]  Paul E. Sawchenko,et al.  Regional Differentiation of the Medial Prefrontal Cortex in Regulating Adaptive Responses to Acute Emotional Stress , 2006, The Journal of Neuroscience.

[27]  G. Koob,et al.  Corticotropin-Releasing Factor within the Central Nucleus of the Amygdala Mediates Enhanced Ethanol Self-Administration in Withdrawn, Ethanol-Dependent Rats , 2006, The Journal of Neuroscience.

[28]  R. Spanagel,et al.  REVIEW: Behavioural assessment of drug reinforcement and addictive features in rodents: an overview , 2006, Addiction biology.

[29]  J. Gibney,et al.  The impact on clinical practice of routine screening for macroprolactin. , 2005, The Journal of clinical endocrinology and metabolism.

[30]  M. Hallett,et al.  Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-Coil , 2005, Clinical Neurophysiology.

[31]  V. Yuferov,et al.  Neuroendocrine alterations in a high-dose, extended-access rat self-administration model of escalating cocaine use , 2003, Psychoneuroendocrinology.

[32]  J. Herman,et al.  The medial prefrontal cortex differentially regulates stress‐induced c‐fos expression in the forebrain depending on type of stressor , 2003, The European journal of neuroscience.

[33]  M. Kreek,et al.  Increased CRH mRNA levels in the rat amygdala during short-term withdrawal from chronic 'binge' cocaine. , 2003, Brain research. Molecular brain research.

[34]  C. Collier,et al.  Salivary cortisol on ROCHE Elecsys immunoassay system: pilot biological variation studies. , 2003, Clinical biochemistry.

[35]  M. Kreek,et al.  Alterations in hypothalamic–pituitary–adrenal axis activity and in levels of proopiomelanocortin and corticotropin-releasing hormone-receptor 1 mRNAs in the pituitary and hypothalamus of the rat during chronic ‘binge’ cocaine and withdrawal , 2003, Brain Research.

[36]  Rita Z. Goldstein,et al.  Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. , 2002, The American journal of psychiatry.

[37]  A. Berardelli,et al.  Motor cortex excitability following short trains of repetitive magnetic stimuli , 2001, Experimental Brain Research.

[38]  M Fahie-Wilson,et al.  Macroprolactin and the Roche Elecsys prolactin assay: characteristics of the reaction and detection by precipitation with polyethylene glycol. , 2000, Clinical chemistry.

[39]  JaneR . Taylor,et al.  Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli , 1999, Psychopharmacology.

[40]  J. Adès,et al.  Benzodiazepine treatment for alcohol-dependent patients. , 1998, Alcohol and alcoholism.

[41]  G F Koob,et al.  Drug abuse: hedonic homeostatic dysregulation. , 1997, Science.

[42]  A. Damasio The somatic marker hypothesis and the possible functions of the prefrontal cortex. , 1996, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[43]  M. Meaney,et al.  The role of the medial prefrontal cortex (cingulate gyrus) in the regulation of hypothalamic-pituitary-adrenal responses to stress , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[44]  G. Gessa,et al.  Marked inhibition of mesolimbic dopamine release: a common feature of ethanol, morphine, cocaine and amphetamine abstinence in rats. , 1992, European journal of pharmacology.

[45]  N. Branston,et al.  The measurement of electric field, and the influence of surface charge, in magnetic stimulation. , 1991, Electroencephalography and clinical neurophysiology.

[46]  P S Tofts,et al.  The distribution of induced currents in magnetic stimulation of the nervous system. , 1990, Physics in medicine and biology.

[47]  Y. Endo [Alcohol-induced Cushing syndrome]. , 1988, Nihon rinsho. Japanese journal of clinical medicine.

[48]  R. Solomon,et al.  An opponent-process theory of motivation. I. Temporal dynamics of affect. , 1974, Psychological review.

[49]  M. Barr,et al.  Brain Stimulation in Alcohol Use Disorders: Investigational and Therapeutic Tools. , 2016, Biological psychiatry. Cognitive neuroscience and neuroimaging.

[50]  Motoaki Nakamura [Therapeutic application of repetitive transcranial magnetic stimulation for major depression]. , 2012, Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica.

[51]  P. Kalivas,et al.  Drug Addiction as a Pathology of Staged Neuroplasticity , 2008, Neuropsychopharmacology.

[52]  H. Smeets,et al.  A functional polymorphism of the mu-opioid receptor gene (OPRM1) influences cue-induced craving for alcohol in male heavy drinkers. , 2007, Alcoholism, clinical and experimental research.

[53]  M. Diana,et al.  The dopamine hypothesis of drug addiction: hypodopaminergic state. , 2005, International review of neurobiology.

[54]  R. Solomon,et al.  An Opponent-Process Theory of Motivation , 1978 .